title: Synaptic neuropeptide release induced by octopamine without Ca2+ entry into the nerve terminal.
abstract: Synaptic release of neurotransmitters is evoked by activity-dependent Ca(2+) entry into the nerve terminal. However, here it is shown that robust synaptic neuropeptide release from Drosophila motoneurons is evoked in the absence of extracellular Ca(2+) by octopamine, the arthropod homolog to norepinephrine. Genetic and pharmacology experiments demonstrate that this surprising peptidergic transmission requires cAMP-dependent protein kinase, with only a minor contribution of exchange protein activated by cAMP (epac). Octopamine-evoked neuropeptide release also requires endoplasmic reticulum Ca(2+) mobilization by the ryanodine receptor and the inositol trisphosphate receptor. Hence, rather than relying exclusively on activity-dependent Ca(2+) entry into the nerve terminal, a behaviorally important neuromodulator uses synergistic cAMP-dependent protein kinase and endoplasmic reticulum Ca(2+) signaling to induce synaptic neuropeptide release.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Dinara
authors.initials: D
authors.lastname: Shakiryanova
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Zettel
authors.forename: Tingting
authors.initials: T
authors.lastname: Gu
authors.forename: Randall S
authors.initials: RS
authors.lastname: Hewes
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Levitan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D009655:Octopamine / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C542725:Epac protein, Drosophila; D020662:Guanine Nucleotide Exchange Factors; D009479:Neuropeptides; D009655:Octopamine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium